Inhibition of cytochrome oxidase activity by local anaesthetics.

Using a polarographic method, we studied the inhibition of mitochondrial electron transport at the cytochrome c oxidase site caused by eight local anaesthetics. The diversity of the types of inhibition observed indicate the importance of electrostatic interactions between the anaesthetic molecules and the membrane protein. A linear relationship was recognized between the anaesthetic activity of infiltration and the affinity for the enzyme. We also observed a significant relationship between this affinity and the octanol-water partition coefficient. This result suggests that lipophilic interactions are involved in cytochrome oxidase-anaesthetic binding. We tried to establish a parallel between this binding and the mechanism of anaesthesia involving the nerve membrane proteins.

Plasma concentrations and pharmacokinetics of misonidazole after intraperitoneal administration to the mouse.

The pharmacokinetics of misonidazole, a hypoxic-cell radiosensitizer, were determinated after intraperitoneal administration to standardized Balb/c mice. The experimental data was fitted, using non linear analysis, to plasma-concentration curves described by tri-exponential equations derived from a two-compartment model. The pharmacokinetic constants (absorption and elimination coefficients) were determinated.

The fate of adenosine monophosphate in the rat after a single oral administration. Influence of a simultaneous treatment by papaverine.

The fate in the organism of Adenosine Monophosphate after a single oral administration of 10 mg/kg, was studied in the Rat, using 14C-labelled AMP. This paper deals more specially with the study of the plasmatic kinetics of AMP, since we proved at first that the AMP molecule goes intact through the intestinal barrier into the blood. The effects on these kinetics of a joint administration of Papaverine are considered.